Recently an adipocyte hormone called leptin has emerged as a potential factor in the regulation of ventilation. The ob/ob knockout mouse is leptin deficient, hyperphagic, obese, hypothermic, but also hypoventilates resulting in an elevated CO2 level at baseline. These mice also have a blunted response to hypercapnia as compared to wild type mice even before the changes in weight occur. Leptin replacement corrects both the hypoventilation and impaired responsiveness. There have been no studies to date in humans evaluating the relationship between leptin and ventilatory responsiveness. In this grant, we propose a series of studies to characterize the influence of leptin on ventilatory control in humans. We hope that one day this information can be used to treat patients with obesity hypoventilation syndrome and other disorders ofventilatory control. [unreadable] [unreadable]